Familial Hypercholesterolaemia (FH) is a genetic disorder leading to an increase in levels of total and low density lipoprotein cholesterol promoting atherosclerosis (ATH) and premature cardiovascular disease (CVD). Inflammation has been considered to be involved in the pathogenesis of CVD, namely the activity of pro-inflammatory cytokines and acute phase proteins. Genetic and oxidative stress markers may contribute to ATH and CVD outcome.
We intended to investigate the role of genetic, inflammatory and oxidative biomarkers in the clinical outcome of FH patients and study its putative correlation with CVD. We selected 41 FH patients with CVD, 91 without CVD and 49 healthy individuals. All individuals were characterized through the determination of the lipid profile (high density lipoprotein, LDL and total cholesterol (TC), triglycerides (TG), apolipoproteinA, apolipoproteinB, lipoprotein(a)), measurement of serum concentration of inflammatory markers (ceruloplasmin, haptoglobin and C reactive protein), pro-inflammatory cytokines (interleukin-6 (IL6) and tumor necrosis factor-alpha (TNFα)), homocysteine and markers of antioxidant / pro-oxidant status (nitric oxid (NO) and oxidized LDL). Genetic characterization was achieved by the study of polymorphisms in the genes encoding for LPL, APOAV, APOCIII, TNF-α, IL6, MTHFR and NOS.
The results showed that the group of FH patients with CVD presented increased TC (p<0,001) and LDL cholesterol (p=0,001) and apoB (p<0,001) levels and decreased apoA1 (p=0,021) levels in relation to the FH group without CVD. In the FH group with CVD it was observed the highest oxLDL and the lowest NO concentrations. APOAV-1131C and APOCIII 3238G allele were associated with higher TG levels (p=0,013; p=0,042) in the FH group without CVD. MTHFR 677T allele was associated with high TC levels (p=0,006) in the FH group with CVD.
Markers of lipid metabolism are evident between the groups analyzed however inflammatory and genetic markers need further studies to improve our knowledge of their role in CVD outcome.